U.S. patent number 9,832,994 [Application Number 14/362,898] was granted by the patent office on 2017-12-05 for thymol and totarol antibacterial composition.
This patent grant is currently assigned to COLGATE-PALMOLIVE COMPANY. The grantee listed for this patent is Laurence Du-Thumm, Rehana Gafur, Regina Hourigan, James Masters, Jairajh Mattai, Shira Pilch. Invention is credited to Laurence Du-Thumm, Rehana Gafur, Regina Hourigan, James Masters, Jairajh Mattai, Shira Pilch.
United States Patent |
9,832,994 |
Hourigan , et al. |
December 5, 2017 |
Thymol and totarol antibacterial composition
Abstract
An antibacterial composition comprising thymol and totarol. This
combination provides synergistic effect against gram negative and
gram positive bacteria.
Inventors: |
Hourigan; Regina (Metuchen,
NJ), Gafur; Rehana (Clifton, NJ), Mattai; Jairajh
(Piscataway, NJ), Masters; James (Ringoes, NJ), Du-Thumm;
Laurence (Princeton, NJ), Pilch; Shira (Highland Park,
NJ) |
Applicant: |
Name |
City |
State |
Country |
Type |
Hourigan; Regina
Gafur; Rehana
Mattai; Jairajh
Masters; James
Du-Thumm; Laurence
Pilch; Shira |
Metuchen
Clifton
Piscataway
Ringoes
Princeton
Highland Park |
NJ
NJ
NJ
NJ
NJ
NJ |
US
US
US
US
US
US |
|
|
Assignee: |
COLGATE-PALMOLIVE COMPANY (New
York, NY)
|
Family
ID: |
45524939 |
Appl.
No.: |
14/362,898 |
Filed: |
December 15, 2011 |
PCT
Filed: |
December 15, 2011 |
PCT No.: |
PCT/US2011/065024 |
371(c)(1),(2),(4) Date: |
June 04, 2014 |
PCT
Pub. No.: |
WO2013/089721 |
PCT
Pub. Date: |
June 20, 2013 |
Prior Publication Data
|
|
|
|
Document
Identifier |
Publication Date |
|
US 20140314689 A1 |
Oct 23, 2014 |
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K
8/34 (20130101); A01N 31/08 (20130101); A61K
8/347 (20130101); A61Q 17/005 (20130101); A61Q
11/00 (20130101); A61K 31/05 (20130101); A61P
31/04 (20180101); A01N 31/08 (20130101); A01N
31/08 (20130101); A01N 2300/00 (20130101); A61K
31/05 (20130101); A61K 2300/00 (20130101); Y02A
50/473 (20180101); Y02A 50/30 (20180101) |
Current International
Class: |
A01N
31/08 (20060101); A61Q 17/00 (20060101); A61K
8/34 (20060101); A61Q 11/00 (20060101); A61K
31/05 (20060101) |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
|
|
|
|
|
|
|
1249929 |
|
Apr 2000 |
|
CN |
|
2011-105635 |
|
Jun 2011 |
|
JP |
|
WO 97/01348 |
|
Jan 1997 |
|
WO |
|
WO 00/69277 |
|
Nov 2000 |
|
WO |
|
WO2005073154 |
|
Aug 2005 |
|
WO |
|
WO2006134160 |
|
Dec 2006 |
|
WO |
|
WO2008085446 |
|
Jul 2008 |
|
WO |
|
WO2010002571 |
|
Jan 2010 |
|
WO |
|
WO2010010320 |
|
Jan 2010 |
|
WO |
|
WO2010046238 |
|
Apr 2010 |
|
WO |
|
WO2010146142 |
|
Dec 2010 |
|
WO |
|
Other References
International Search Report and the Written Opinion issued in
International Application PCT/US2011/065024 dated Nov. 9, 2012. WO.
cited by applicant .
Biochimica et Biophysica Acta (BBA)--Biomembranes vol. 1511, Issue
2, Apr. 2, 2001, pp. 281-290:
http://www.sciencedirect.com/science/article/pii/S000527360100284X.
cited by applicant .
Smith E., et al., "The Phenolic Diterpene Totarol Inhibits
Multidrug Efflux Pump Activity in Staphylococcus aureus.
Antimicrobial Agents and Chemotherapy," Dec. 2007, p. 4480-4483,
vol. 51, No. 12. cited by applicant .
Jaiswal R., et al., "Totarol Inhibits Baterial Cytokinesis by
Perturbing the Assembly Dynamics of FtsZ. Biochemistry," 46 (14),
4211-4220, 2007. cited by applicant .
"Totarol is a phenolic diterpene extracted from the heartwood of
the totara tree by the use of an organic solvent or near critical
fluid, commercially available preparations using CO2. The resultant
extract shows good antibacterial activity but needs to be included
with a fungicide to offer complete protection against microbial
contamination." Source:
http://www.personalcaremagazine.com/Story.aspx?story=4456. cited by
applicant .
"Totarol, an extract from totara wood, has been shown to inhibit to
multi-drug efflux pump of Staphylococcus aureus and sub-inhibitory
concentrations were found to reduce the MICs of selected
antibiotics. These results hold the promise of the use of plant
extracts that may allow reduced concentrations of synthetic
preservatives by potentiating their activity by blocking the effect
of efflux pumps."
http://www.personalcaremagazine.com/Story.aspx?Story=4456. cited by
applicant .
K. Roden, "Natural Preservatives: myth or magic?" Personal Care
Magazine, Nov. 2008. Internet at:
http://www.personalcaremagazine.com/Story.aspx?story=4456 (6
pages). cited by applicant.
|
Primary Examiner: Parad; Dennis J
Claims
What is claimed is:
1. A method of controlling gram negative bacteria comprising
contacting the gram negative bacteria with a composition comprising
thymol and totarol, wherein a weight ratio of thymol to totarol is
5:1 to 1:5, and a Fractional Inhibition Concentration (FIC) Value
of thymol and totarol is 0.6 or less.
2. The method of claim 1, wherein the gram negative bacteria is E.
coli.
3. The method of claim 1, wherein the weight ratio of thymol to
totarol is 3.21:1 to 1:3.21, and the Fractional Inhibition
Concentration (FIC) Value of thymol and totarol is 0.26 or
less.
4. The method of claim 1, wherein the weight ratio of thymol to
totarol is 1.56:1 to 1:1.56, and the Fractional Inhibition
Concentration (FIC) Value of thymol and totarol is 0.10 or
less.
5. A method of controlling gram positive bacteria comprising
contacting the gram negative bacteria with a composition comprising
thymol and totarol, wherein a weight ratio of thymol to totarol is
1.56:1 to 1:1.56, and a Fractional Inhibition Concentration (FIC)
Value of thymol and totarol is 0.41 or less.
6. The method of claim 5, wherein the gram positive bacteria is S.
aureus.
Description
CROSS-REFERENCE TO RELATED PATENT APPLICATIONS
The present application is a U.S. national stage entry under 35
U.S.C. .sctn.371 of Patent Cooperation Treaty Patent Application
No. PCT/US2011/65024, filed Dec. 15, 2011, the entirety of which is
incorporated herein by reference.
FIELD OF THE INVENTION
The present invention relates to antibacterial compositions.
BACKGROUND OF THE INVENTION
Control of bacteria in products and on surfaces where products are
used is an ongoing challenge. For example, E. coli is a challenging
bacterium to control. Compared to gram positive bacteria, E. coli
is a gram negative bacterium having an additional outer membrane
and higher amounts of peptidoglycan in the cell wall. This is what
makes E. coli more challenging to control. While some materials are
known to provide some antibacterial effect, it is desired to
develop improvements in these materials. One such improvement would
be to provide bacterial kill while using less material.
BRIEF SUMMARY OF THE INVENTION
An antibacterial composition comprising thymol and totarol. This
combination is synergistic for these two materials such that a
lesser amount of either can be used.
Further areas of applicability of the present invention will become
apparent from the detailed description provided hereinafter. It
should be understood that the detailed description and specific
examples, while indicating the preferred embodiment of the
invention, are intended for purposes of illustration only and are
not intended to limit the scope of the invention.
DETAILED DESCRIPTION OF THE INVENTION
The following description of the preferred embodiment(s) is merely
exemplary in nature and is in no way intended to limit the
invention, its application, or uses.
An antibacterial composition comprising thymol and totarol. The
combination of thymol with totarol provides synergistic effect,
which requires less of either material as compared to each material
alone. The synergistic effect is effective against gram negative
bacteria, such as E. coli, and gram positive bacteria, such as S.
aureus.
Synergism is found when the fractional inhibitory concentration,
which is calculated below, is found to be less than or equal to
0.75.
In certain embodiments, the weight ratio of thymol to totarol is
5:1 to 1:5. In other embodiments, the weight ratio is 3.21:1 to
1:3.21 or 1.56:1 to 1:1.56. In other embodiments, the weight ratio
of thymol to totarol is one of 5:1, 1:5, 3.21:1, 1:3.21, 1.56:1,
1:1.56, or 1:1.
In the 1.56:1 to 1:1.56 range, the combination of thymol and
totarol is synergistic for both the gram negative bacteria E. coli
and the gram positive bacteria S. aureus.
In certain embodiments, the amount of thymol in the composition is
0.0001 to 2% by weight of the composition. In other embodiments,
the amount is 0.0001 up to 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3,
0.2, or 0.1% by weight of the composition. In other embodiments,
the amount is 0.0001 up to 0.5, 1, 1.5, or 2% by weight. In other
embodiments, the amount is 0.0001 to 1% or 0.0001 to 0.5% by weight
of the composition. In another embodiment, the amount is 0.5% by
weight.
In certain embodiments, the amount of totarol in the composition is
0.0001 to 2% by weight of the composition. In other embodiments,
the amount is 0.0001 up to 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3,
0.2, or 0.1% by weight of the composition. In other embodiments,
the amount is 0.0001 up to 0.5, 1, 1.5, or 2% by weight. In other
embodiments, the amount is 0.0001 to 1% or 0.0001 to 0.5% by weight
of the composition. In another embodiment, the amount is 0.5% by
weight.
This antibacterial combination of thymol and totarol is useful in
personal care, oral care, and home care compositions. Examples of
personal care compositions include, but are not limited to, body
wash/shower gel, liquid hand cleanser, bar soap, shampoo,
conditioner, antiperspirant/deodorants, and cosmetics. Examples of
oral care compositions include, but are not limited to,
dentifrices, toothpastes, tooth powders, prophylaxis pastes, mouth
rinses, lozenges, gums, gels, paints, confectionaries, and denture
cleaners. Examples of home care compositions include, but are not
limited to, dish liquids, dish pastes, hard surface cleaners,
fabric conditioners, and laundry detergents.
In certain embodiments, the thymol and totarol can be present in a
body wash/shower gel, liquid hand cleanser, or shampoo in which
each of these compositions include a surfactant. The thymol and
totarol can also be included in a soap (fatty acid soap), which can
be in the shape of a bar soap.
EXAMPLES
Minimum Inhibition Concentration (MIC)
Serial dilutions of the active are combined with tryptic soy broth
and 0.1 optical density of bacteria in a 96 well plate. The optical
density of the mixture is measured after 16-24 hours at 37.degree.
C. An increase in optical density represents bacterial growth. The
plate is analyzed to determine the minimum concentration needed to
inhibit growth of bacteria. Numbers are reported in ppm. The MIC
values are determined for thymol and totarol against E. Coli and S.
aureus. The MIC dose response assay is conducted just as the MIC,
however, one active's concentration is kept constant and the other
active's concentration follows a two-fold serial dilution.
Fractional Inhibition Concentration (FIC)
The MIC values are also determined for thymol in the presence of
totarol to determine the Fractional Inhibitory Concentration (FIC).
This calculation accounts for the fractional activity of thymol and
totarol within a MIC test.
.times..times..times..times..times..times..times..times..times..times..ti-
mes..times..times..times..times..times..times..times..times..times..times.-
.times..times..times..times..times..times..times..times..times..times..tim-
es. ##EQU00001## such that:
TABLE-US-00001 FIC Value Equivalant x .ltoreq. 0.75 Synergism 0.75
< x .ltoreq. 1.3 Additive x .gtoreq. 1.3 Antagonistic
TABLE-US-00002 TABLE 1 MIC and FIC Values for Thymol and Totarol
Actives E. coli S. aureus Thymol 125 ppm 125 ppm Totarol 125 ppm
31.25 ppm Mixture (fixed 62.5 ppm thymol + 62.5 ppm thymol + ratio
of thymol:totarol 12.5 ppm totarol 12.5 ppm totarol 5:1) FIC Value
0.6 0.9 Thymol 125 ppm 125 ppm Totarol 125 ppm 31.25 ppm Mixture
(ratio of 62.5 ppm totarol + 31.25 ppm totarol + totarol:thymol
12.5 ppm thymol 6.25 ppm thymol 5:1) FIC Value 0.6 1.05 Thymol 125
ppm 31.25 ppm Totarol 125 ppm 31.25 ppm Mixture (ratio of 7.8 ppm
thymol + 7.8 ppm thymol + thymol:totarol 5 ppm totarol 5 ppm
totarol 1.56:1) FIC Value 0.10 0.41 Thymol 125 ppm 31.25 ppm
Totarol 125 ppm 31.25 ppm Mixture (ratio of 7.8 ppm totarol + 7.8
ppm totarol + totarol:thymol: 5 ppm thymol 5 ppm thymol 1.56:1) FIC
Value 0.10 0.41 Thymol 125 ppm 31.25 ppm Totarol 125 ppm 31.25 ppm
Mixture (ratio of 7.8 ppm thymol + 7.8 ppm thymol + totarol:thymol
25 ppm totarol 25 ppm totarol 3.21:1) FIC Value 0.26 1.04 Thymol
125 ppm 31.25 ppm Totarol 125 ppm 31.25 ppm Mixture (ratio of 7.8
ppm totarol + 7.8 ppm totarol + thymol:totarol: 25 ppm thymol 25
ppm thymol 3.21:1) FIC Value 0.26 1.04
As can be seen from the table, the combination of thymol to totarol
is synergistic for the gram negative bacteria E. coli in a 5:1
ratio to a 1:5 ratio. Also, when varying the ratio of thymol to
totarol closer to 1:1, there is a broad spectrum synergistic
activity against both the gram negative and the gram positive
bacteria.
As used throughout, ranges are used as shorthand for describing
each and every value that is within the range. Any value within the
range can be selected as the terminus of the range. In addition,
all references cited herein are hereby incorporated by referenced
in their entireties. In the event of a conflict in a definition in
the present disclosure and that of a cited reference, the present
disclosure controls.
Unless otherwise specified, all percentages and amounts expressed
herein and elsewhere in the specification should be understood to
refer to percentages by weight. The amounts given are based on the
active weight of the material.
* * * * *
References